The present application is generally related to controlling deep brain stimulation using a closed-loop system that compensates for changes in sensor sensitivity for neurotransmitter levels that result from glial scarring.
Deep brain stimulation (DBS) refers to the delivery of electrical pulses into one or several specific sites within the brain of a patient to treat various neurological disorders. For example, DBS has been proposed as a clinical technique for treatment of chronic pain, essential tremor, Parkinson's disease (PD), dystonia, epilepsy, depression, obsessive-compulsive disorder, and other disorders.
A DBS procedure typically involves first obtaining preoperative images of the patient's brain (e.g., using computer tomography (CT) or magnetic resonance imaging (MRI)). The imaging process sometimes involves first affixing to the patient's skull fiducial markers that are discernable on the images produced by the imaging process. The fiducial markers assist in registering the preoperative images to the actual physical position of the patient in the operating room during the subsequent surgical procedure. Using the preoperative images, the neurosurgeon can select a target region within the brain, an entry point on the patient's skull, and a desired trajectory between the entry point and the target region. The entry point and trajectory are carefully selected to avoid intersecting or otherwise damaging critical brain structures.
In the operating room, the patient is immobilized and the patient's actual physical position is registered. The physician marks the entry point on the patient's skull and drills a burr hole at that location. A mechanism is provided to precisely control the path through the patient's brain to the desired location. Specifically, a positioning error on the order of a millimeter can have a significant negative effect on the efficacy of the DBS therapy. Stereotactic instrumentation and trajectory guide devices are commercially available products that facilitate the control of the trajectory and positioning of a lead during the surgical procedure.
A microdrive introducer can be used to insert a deep brain stimulation lead toward the selected region of the brain along the selected trajectory. The lead provides one or several conductive paths to deliver stimulation pulses to the selected region. The lead includes a very small diameter insulative lead body with one or several conductors (e.g., stranded wires) embedded in the insulative material. The lead also includes one or several electrodes at a distal end of the lead that are electrically coupled to respective conductors. The electrodes can be used to record signals within the brain and/or to deliver electrical stimulation pulses to brain tissue. Often, the electrical activity adjacent to one or several electrodes is analyzed to determine whether the recorded signals are consistent with the targeted region of the brain. If the recorded signals are not consistent with the targeted region, an adjustment to the lead's position can be made as appropriate.
After the correct location for the stimulation is established, an implantable pulse generator is implanted within a subcutaneous region and the stimulation lead is implanted underneath the skin and “tunneled” to the location of the pulse generator. The pulse generator is “programmed” to deliver electrical stimulation according to various stimulation parameters such as pulse amplitude, pulse width, pulse frequency, electrode configuration, etc. In conventional DBS therapies, stimulation is provided on a chronic basis. That is, electrical stimulation pulses are provided to the patient on a substantially continuous basis.
More recent DBS therapies have been proposed that utilize closed-loop feedback systems to control when to deliver electrical stimulation and to control the stimulation parameters. For example, a number of systems to treat epilepsy have been proposed in which electrical activity within various regions of the brain are sensed and electrical stimulation is applied when an epileptic event is imminent as indicated by frequency specific oscillations in the electrical activity. Closed-loop systems that measure neurotransmitter levels in lieu of electrical activity have been alternatively proposed. For Parkinson's disease, it has been proposed to measure the amount of extracellular glutamate in certain regions of the brain and control electrical stimulation applied to the thalamic tissue in response to the measured glutamate level. It has also been proposed to employ a closed-loop system to selectively apply electrical stimulation to a patient suffering from depression based upon the amount of serotonin in various regions of the brain. Appetite suppression using electrical stimulation to treat obesity is another therapy that could benefit from the measurement of neurotransmitter levels.